Glypican 3 was separated in the small intestine of a rat as a transcript in a developmental stage (Mol. Cell Biol. 8, 4243-4249, 1988), and thereafter, it was reported that a gene encoding glypican 3 was isolated from a glycosyl-phosphatidylinositol (GPI)-linked type sulfate human gastric cancer cell line having a core protein of a glypican family (molecular weight of 69 kDa) (Gene, 188, 151-156, 1997). It was reported that glypican 3 forms a protein-protein complex together with an insulin-like growth factor-2 and regulates actions of the insulin-like growth factor-2 (Nat. Genet., 12, 241-247, 1996). Particularly, it was known that glypican 3 is expressed in the fetal liver and placenta during development and in normal adult tissue, expression of glypican 3 is deteriorated or glypican 3 is not expressed at all.
Glypican 3 is known as a kind of oncofetal antigen that belongs to a glypican family of glycosyl-phosphatidylinositol (GPI)-anchored heparin sulfate proteoglycans, and cell membrane-bound glypican 3 is known to be composed of two subunits linked by one or more disulfide bonds.
In relation to functions and uses of glypican 3, it was reported that glypican may serve as a hepatocellular carcinoma marker, and it was suggested that glypican may serve as a receptor of endostatin having a possibility of an angiogenesis inhibitor, which was not clearly identified.
Recently, it has been known that glypican 3 is expressed in various cancers, particularly, hepatocellular carcinoma (HCC), melanoma, Wilm's tumor, and hepatoblastoma (Jakubovic and Jothy; Ex. Mol. Path. 82:184-189 (2007); Nakatsura and Nishimura, Biodrugs 19(2):71-77 (2005)), and it was reported that it is actually possible to treat tumors such as hepatic cancer, and the like, using an antibody against glypican 3 (Korean Patent No. 877,176, and the like).
Currently, several anti-glypican 3 antibodies were reported, but an antibody having a satisfactory therapeutic effect, particularly, an excellent cancer therapeutic effect has been not yet reported. Therefore, a need for an anti-glypican 3 antibody having a more excellent therapeutic effect is significant.
Therefore, the present inventors invented a novel antibody specifically binding to glypican 3 with high affinity, and confirmed a possibility of the antibody according to the present invention as an efficient anti-cancer agent, thereby completing the present invention.